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Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma.

Johnson-VJ; Yucesoy-B; Luster-MI
J Allergy Clin Immunol 2005 Oct; 116(4):851-858
IL-1 is a pleotropic cytokine that has been shown to play a prominent role in asthma induced by large-molecular-weight proteins. Increased IL-1 immunostaining in the submucosa of patients with toluene diisocyanate (TDI)-induced asthma has also been observed, suggesting that this cytokine might also be important in asthma associated with low-molecular-weight chemicals. We sought to determine the role of IL-1 signaling in airway reactivity and inflammation by using a murine model of TDI-induced asthma. C57BL/6 mice were exposed to TDI by means of vapor inhalation (20 ppb; 4 hours per day, 5 days per week, for 6 weeks) and then challenged 2 weeks later by inhalation with 20 ppb TDI vapor for 1 hour. Sensitized-challenged mice showed increased airway hyperresponsiveness (AHR), increased levels of TDI-specific IgG1 antibodies, airway epithelial thickening, inflammation consisting of infiltrating lymphocytes and eosinophils, and increased mRNA expression of IL-4, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the lung. Prevention of IL-1 signaling through deletion of the IL-1 receptor type I or administration of neutralizing antibodies to both IL-1beta and IL-1alpha abrogated the development of TDI-induced asthma. A partial reduction in AHR and TDI-specific IgG1 levels was observed in mice administered anti-IL-1beta, whereas anti-IL-1alpha had no effect on either parameter. Antibodies to IL-1beta or IL-1alpha alone blocked airway inflammation and the expression of IL-4 and adhesion molecules in the lung. These results suggest that IL-1 signaling is critical for AHR and airway inflammation, with IL-1beta and IL-1alpha having unique and overlapping roles in TDI-induced occupational asthma.
Models; Bronchial-asthma; Toluenes; Airway-obstruction; Airway-resistance; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment
Victor J. Johnson, PhD, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd, Mail Stop 3014, Morgantown, WV 26505-2888
Publication Date
Document Type
Journal Article
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Fiscal Year
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NIOSH Division
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
Journal of Allergy and Clinical Immunology
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division